Abstract
Aggregated alpha-synuclein proteins form brain lesions that are hallmarks of neurodegenerative synucleinopathies, and oxidative stress has been implicated in the pathogenesis of some of these disorders. Using antibodies to specific nitrated tyrosine residues in alpha-synuclein, we demonstrate extensive and widespread accumulations of nitrated alpha-synuclein in the signature inclusions of Parkinson's disease, dementia with Lewy bodies, the Lewy body variant of Alzheimer's disease, and multiple system atrophy brains. We also show that nitrated alpha-synuclein is present in the major filamentous building blocks of these inclusions, as well as in the insoluble fractions of affected brain regions of synucleinopathies. The selective and specific nitration of alpha-synuclein in these disorders provides evidence to directly link oxidative and nitrative damage to the onset and progression of neurodegenerative synucleinopathies.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alzheimer Disease / metabolism
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Alzheimer Disease / pathology
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Antibodies, Monoclonal
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Blotting, Western
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Brain / metabolism*
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Brain / pathology
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Brain Chemistry
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Enzyme-Linked Immunosorbent Assay
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Fluorescent Antibody Technique
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Humans
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Immunohistochemistry
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Lewy Bodies / chemistry
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Lewy Body Disease / metabolism
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Lewy Body Disease / pathology
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Microscopy, Immunoelectron
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Multiple System Atrophy / metabolism
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Multiple System Atrophy / pathology
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Nerve Tissue Proteins / analysis
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Nerve Tissue Proteins / immunology
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Nerve Tissue Proteins / metabolism*
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Neurodegenerative Diseases / metabolism*
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Neurodegenerative Diseases / pathology*
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Neurons / chemistry
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Neurons / metabolism
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Neurons / ultrastructure
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Oxidative Stress*
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Parkinson Disease / metabolism
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Parkinson Disease / pathology
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Synucleins
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Tyrosine / analogs & derivatives*
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Tyrosine / analysis
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Tyrosine / immunology
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Tyrosine / metabolism*
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alpha-Synuclein
Substances
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Antibodies, Monoclonal
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Nerve Tissue Proteins
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SNCA protein, human
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Synucleins
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alpha-Synuclein
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3-nitrotyrosine
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Tyrosine